Targeting the epidermal growth factor receptor in high-grade glioma

Lead PI: Prof Terry Johns, Hudson Institute of Medical Research, VIC

Research Idea

Using novel patient-derived tumour cell lines, the team will determine why EGFR-targeted therapeutics have failed as a treatment for high-grade glioma and develop strategies for effectively using EGFR-targeted drugs.

Problem

Epidermal growth factor receptor (EGFR) is altered in about 60% of high-grade glioma; therefore, it is logical that targeting EGFR would be a successful strategy for treating high-grade glioma. However, clinical trials with EGFR-targeted therapeutics have been a failure. The team are trying to understand the reasons why these therapeutics have failed and to develop novel strategies for their effective use in patients.

Solution

The group have developed a range of patient-derived HGG cell lines that contain different mutations of EGFR. This unique collection of cells will allow them to determine the mechanisms of resistance to EGFR-targeted therapeutics.

"This project is around trying to understand why brain cancer patients don’t respond and then maybe what we can combine these EGFR drugs with to make them more responsive and effective in brain cancer patients."

- Prof Terry Johns

Why now?

Recent advances allow the team to take HGG cells from patients and grow them in the laboratory in a way that preserves the features of the original tumour. These cells can also be grown in the brains of mice, where they accurately mimic the original tumour. They have established a large panel of these cell lines, which makes this project possible for the first time.

Approach

If successful, the team aim to conduct a clinical trial using the therapeutic approaches established by their research.

Team & Partners

Dr Jacqueline Donoghue, Hudson Institute of Medical Research

Dr Sam Greenall, Hudson Institute of Medical Research

Dr Tim Adams, CSIRO

Prof Paul Mischel, Ludwig Institute for Cancer Research, San Diego.

Impact

If successful, this project will extend the progression-free survival of patients with high-grade glioma.

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